Most Closely HLA-Matched CTLs for Relapsed Epstein Barr Virus(EBV)-Associated Diseases
MALTED
Most Closely HLA-Matched Allogeneic LMP1/2-Specific Cytotoxic T Lymphocytes for Treatment of Patients With Relapsed EBV-Associated Diseases
2 other identifiers
interventional
37
1 country
2
Brief Summary
Patients have a type of a lymph node cancer called lymphoma, a tumor of the nasal passages called nasopharyngeal carcinoma (NPC), a tumor of a particular type of muscle called leiomyosarcoma (LMS) or a condition called severe chronic active EBV (SCAEBV) syndrome. The disease has come back, may come back or has not gone away after treatment. This voluntary research study uses special immune system cells called LMP-specific cytotoxic T lymphocytes, a new experimental therapy. Some patients with these diseases show evidence of infection with the virus that causes infectious mononucleosis (called Epstein-Barr virus, or EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of up to half of the patients with lymphomas, and in some cases of NPC and LMS, suggesting that it may play a role in causing these diseases. Those cancer cells (as well as some B cells in SCAEBV) that are infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if special white blood cells, called T cells, that have been trained to kill cells infected by EBV can survive in the blood and affect the tumor. This treatment with specially trained T cells has had activity against these viruses when the cells are made from patients with those diseases (or, after bone marrow transplant, from the patient's transplant donor). However, sometimes it is not possible to grow these cells; other times, it may take 2 to 3 months to make the cells, which may be too long when one has an active tumor. We are therefore asking if subjects would like to participate in this study, which tests if blood cells from a donor that is a partial match with the subject (or the transplant donor) that have been grown in the way described above can survive in the blood and affect the disease. These LMP-specific CTLs are an investigational product not approved by the Food and Drug Administration.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Feb 2012
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 12, 2011
CompletedFirst Posted
Study publicly available on registry
October 5, 2011
CompletedStudy Start
First participant enrolled
February 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
January 22, 2020
CompletedFebruary 7, 2020
February 1, 2020
3.1 years
August 12, 2011
February 5, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Patients with dose limiting toxicities after T-cell infusions
To determine the safety of intravenous injections of third-party, partially HLA- matched, allogeneic Epstein Barr Virus (EBV)-specific cytotoxic T-lymphocytes (CTL) in patients with severe chronic active EBV (SCAEBV) infection or EBV-associated Hodgkin or non-Hodgkin lymphomas (HL/NHL), other lymphoproliferative disorders (LPD) or other malignancies (leiomyosarcoma and nasopharyngeal carcinoma)
6 weeks
Secondary Outcomes (3)
Safety and response to a repeated dosage regimen
5 years
Analysis of immune function of CTLs
5 years
Number of patients with an EBV and/or disease response to the CTLs
6 weeks
Study Arms (1)
LMP Specific T cells
EXPERIMENTALLMP specific T cells will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line and the IV flushed with saline. The volume of infusion will depend upon the concentration of the cells when frozen, the dose level, and the size of the patient.
Interventions
Three dose levels will be evaluated: Dose Level 1: 2×10\^7 cells/m2; Dose Level 2: 1×10\^8 cells/m2; Dose Level 3: 2×10\^8 cells/m2 If patients have a partial response or have stable disease they will be eligible to receive up to 5 further doses of CTLs, each of which will consist of the same number as their first injection.
Eligibility Criteria
You may qualify if:
- SCREENING:
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma - Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma - Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (\> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
- Karnofsky/Lansky score 50% or more.
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy.
- TREATMENT:
- Any patient, regardless of age or sex, with one or more of the following EBV-positive or associated disorders, regardless of the histological subtype: - Hodgkin lymphoma - Non-Hodgkin lymphoma - Lymphoproliferative disorder - Nasopharyngeal carcinoma - Leiomyosarcoma - Severe chronic active EBV infection syndrome (SCAEBV), defined as high EBV viral load in plasma or PBMC (\> 4000 genomes per ug PBMC DNA) and/or biopsy tissue positive for EBV
- The disease needs to be in one of the following stages: - At diagnosis or in first relapse AND the patient is unable to receive conventional chemotherapy for his/her condition. - In second or subsequent relapse. - With residual disease after autologous, syngeneic or allogeneic HSCT.
- Life expectancy 6 weeks or more.
- Tumor tissue is positive for EBV.
- Karnofsky/Lansky score 50% or more.
- Bilirubin less than 3 times higher than the normal limits, AST less than 5 times higher than the normal limits, Hgb greater than 8.0 g/dL and serum creatinine less than 3 times higher than the normal limits.
- Pulse oximetry of greater than 90% on room air.
- If post allogeneic HSCT, patient must not have less than 50% donor chimerism in either peripheral blood or bone marrow.
- Clinical status at enrollment to allow tapering of steroids to less than 0.5 mg/kg/day prednisone at time of treatment.
- Informed consent explained to and signed by patient or parent/guardian able to give informed consent and given a copy.
- +1 more criteria
You may not qualify if:
- SCREENING:
- \. Known HIV positivity.
- TREATMENT:
- Currently receiving any investigational agents or have received any tumor vaccines within previous 4 weeks.
- Active acute grade III-IV graft-versus-host disease.
- Severe intercurrent infection.
- Received alemtuzumab or other anti-T-cell antibody within 28 days.
- HIV seropositivity.
- Pregnancy (due to unknown effects of this therapy on a fetus) or lactation.
- Tumor in a location where enlargement could cause airway obstruction.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Houston Methodist Hospital
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carlos A Ramos, MD
Baylor College of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
August 12, 2011
First Posted
October 5, 2011
Study Start
February 1, 2012
Primary Completion
March 1, 2015
Study Completion
January 22, 2020
Last Updated
February 7, 2020
Record last verified: 2020-02